Self-injurious behavior (SIB) is among the most serious problems among institutionalized populations. It is a feature of autism and present in 7-40% of institutionalized mentally retarded psychotic patients. SIB is assumed to be untreatable and is expensive to manage with costs estimated between $100,000-500,000/year/patient. When present, SIB may be the central reason limiting access to least restrictive settings. Recent evidence has implicated the endogenous opiate system in SIB. Naloxone (an injected opioid blocker) was reported effective in 5 of 6 studies and more recently, naltrexone (an orally administered opioid blocker) has been effective in 10 of 11 reports. Thus, the first promising treatment for SIB appears to be available. However, all of the studies conducted have been acute treatment trials in small numbers of patients. Only one patient has been treated for more than 21 days and the results in this patient were dramatically successful. This purpose of this proposal is to determine the efficacy of naltrexone in the long term (2, 90 day) treatment of SIB. In a placebo-controlled, double-blind reversal design, patients already determined to be responders to naltrexone will receive daily treatment at the most effective dose or placebo. Open placebo washout periods of one month will follow each treatment-placebo period. Behavior will be observed with videotape and scored with a computer-assisted program developed for SIB. Scales will be administered for measuring autistic behavior, various maladaptive behaviors, sleep, neurological status and learning and memory. Plasma will be collected during each treatment-placebo period for measuring B-endorphin (endogenous opiate), related neuropeptides (ACTH, CRH) and cortisol. The results of this study will assist in determining the efficacy of naltrexone in SIB and possible side-effects. In addition to within comparisons of placebo and naltrexone, patients who did not respond, positively will be observed as a positive control group.